tbuckley/cabot-search huggingface dataset:
Preliminary results of a phase IB study of olaparib with concomitant radiotherapy in locally advanced/unresectable soft-tissue sarcoma from the French Sarcoma Group.
Authors: Paul Sargos, Marie Pierre Sunyach, Anne Ducassou, Carmen Llacer, Carine A. Bellera, Audrey Michot, Thibaud Valentin, Nelly Firmin, Jean-Yves Blay, Derek Dinart, Antoine Italiano
Journal: Journal of Clinical Oncology (2022)

11522 Background: The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib (O) has radiosensitizing properties in several tumor models including sarcomas. We studied safety and activity of O with external beam radiation therapy (EBRT) in patients with locally advanced soft-tissue sarcomas (STS). Methods: This phase I study first assessed four dose levels (DL1:25 mg, DL2:50 mg, DL3:100 mg, DL4:150 mg BID) of O administered in combination with EBRT (59.4 Gy in 33 fractions of 1.8 Gy) using a TITE-CRM design. Next, we recruited 15 additional patients in an expansion cohort to assess the tumor response or the histological response for patients with resectable disease. Tumor response was assessed by investigators according to RECIST 1.1 criteria. Results: A total of 41 patients (17 men, 24 women) were enrolled in both cohorts, of whom 19 (46.3%) underwent post-treatment surgery. We observed 1 DLT at DL1 (n = 5), 1 at DL2 (n = 7), 0 at DL3 (n = 11) and 1 at DL4 (n = 3) during the dose escalation. The recommended dose (RP2D) was 100 mg BID. Most common adverse events related to O and/or EBRT were acute dermatitis (G1/2 63.4% of patients, G3/4 34.1%), edema limbs (G1/2 36.6%), fatigue (G1/2 36.6%), nausea (G1/2 31.7%) and myositis (G1/2 29.3%). Among the 22 patients assessed for tumor response, 3 unconfirmed partial responses, 12 stable diseases, 5 progressive diseases, and 2 non-evaluable responses were recorded as best overall responses. The 6-month non-progression rate in that population was 9.1% [95%CI 1.1%-29.2%]. Six (31.6%) good histological responses and 9 (47.4%) poor responses were observed on the 19 patients who underwent surgery (4 responses non-available). Conclusions: This study shows that the combination of O with EBRT is well tolerated and lead to encouraging downstaging. A little less than half of the population was able to benefit from surgery with positive results in more than 30% of the cases and the rest of the population showed a promising stability of the disease at 6 months. We are currently awaiting a minimum of one year follow-up for the expansion cohort to assess survival. Clinical trial information: NCT02787642.
Klotho-derived peptide 6 ameliorates diabetic kidney disease by targeting Wnt/β-catenin signaling
Authors: Xiaowen Chen, Huishi Tan, Jie Xu, Yuan Tian, Qian Yuan, Yangyang Zuo, Qiyan Chen, Xue Hong, Haiyan Fu, Fan Fan Hou, Lili Zhou, Youhua Liu
Journal: Kidney International (2022)
The long term result and efficacy of endoscopic treatment of vesicoureteric reflux using dextranomer / hyaluronic acid: Over 15-year experience in a single-center
Authors: S.T. Ahn, S.B. Cho, H.S. Lee, D.E. Han, J.W. Kim, M.M. Oh, H.S. Park, D.G. Moon
Journal: European Urology (2022)
Discrimination of mucinous pancreatic cysts using an enzymatic turnover assay to improve clinical diagnostic accuracy.
Authors: Daniel Sheik, Vallabh Suresh, Kaleb Byers, U. Chinna Rajesh, Francesco Caiazza, Gina Zhu, Charles Craik, Kimberly S. Kirkwood, V. Jo Davisson
Journal: Journal of Clinical Oncology (2022)

4151 Background: One impact of medical imaging technology has been an approximately 3-fold increase in the incidental detection of pancreatic cysts during routine clinical examinations. To reduce burden on the healthcare system and patients, clinicians desire accurate classification of pancreatic cysts into benign non-mucinous or potentially malignant, mucinous populations. Using EUS-FNA, fluid from these cysts can provide molecular biomarkers of predictive value. However, current in vitro diagnostics lack the desired sensitivity and specificity for clinicians to accurately stratify patients for risk of pre-malignant cancers. This situation can be improved by introducing new biomarkers and novel assay platforms. An enzymatic biomarker, pepsin C, has shown high accuracy for diagnosing mucinous cysts. The use of enzymatic activity assays is applicable to clinical workflows without disruption of current standards of care. Methods: A pepsin C activity assay using a magnetic bead-based platform was developed, with both fluorescent and surface-enhanced Raman spectroscopy (SERS) readouts. The assay platform utilizes selective peptide substrates, and a dimeric Rhodamine-6G-based dye, which allows ultrasensitive detection and significantly decreases the sample volume requirement for analysis, down to 1 µL of cyst fluid. The dye-labeled substrate is immobilized on magnetic beads and reacted with enzyme-containing samples to produce a quantitative assay signal that is standardized and expressed in true enzyme activity units. Results: While both readouts were quantitative and produced linear standard curves, SERS-based analysis was more robust against established biological matrix effects than fluorescence. Nevertheless, both assay modes successfully differentiated mucinous and non-mucinous cysts in a retrospective cohort of 69 cyst fluid samples. Compared with the standard of care CEA assay, this activity-based assay displays much improved sensitivity in diagnosing mucinous pancreatic cysts (Table). Conclusions: This pepsin c activity assay differentiates between mucinous and non-mucinous cysts better than the CEA assay and provides a quantifiable standardized readout. This work establishes a path to a true rule-out assay enabling clinicians to better stratify patients into low risk vs. potential malignancy thus impacting treatment and monitoring plans. [Table: see text]
Transdisciplinary research in energetics and cancer (TREC) training program for early career investigators.
Authors: Melinda L. Irwin, Diana Lowry, Marian L. Neuhouser, Curtis Henry, Dorothy Sears, Kathryn Schmitz, Linda Nebeling, Jennifer A. Ligibel
Journal: Journal of Clinical Oncology (2022)

11031 Background: Given the rising prevalence of obesity, poor diet and physical inactivity, known in combination as “energy balance” or “energetics”, as well as their associations with cancer incidence and mortality, innovative research, clinical care and training of scientists are needed to lower the prevalence of these risk factors and in turn, lower cancer incidence and mortality rates. Methods: With NCI support (R25CA203650) from 2016-2021, we developed and offered an annual one-week, in-residence Transdisciplinary Research in Energetics and Cancer (TREC) Training workshop, followed by a yearlong mentoring program, that focused on energy balance and cancer research across the cancer control continuum. Results: We recruited, educated, trained and mentored 123 early career investigators (TREC Fellows) from 64 different institutions and from diverse academic backgrounds (i.e., 20% basic, 33% clinical and 47% population sciences) in transdisciplinary research in energetics and cancer. Fellows accepted to the TREC Training Program worked with more than 20 expert international TREC Faculty on developing grant applications and original research toward key gaps in energy balance and cancer research. TREC Fellows have published over 270 manuscripts in peer-reviewed journals, with at least 62 published manuscripts including the TREC Fellow as first or senior author and including a TREC Faculty and/or Fellow as co-author. Since completing the Program, TREC Fellows have received at least 31 extramural grants, as principal investigator. Building upon the strengths of the previous five years, we were awarded a competitive renewal to continue the TREC Training Program through 2026. TREC Training program goals are: (1) to continue to offer a TREC Training Program for ̃100 academically diverse early career investigators including a 5-day in-residence workshop focused on the Fellows research, networking, mentoring and professional development; (2) to evaluate the TREC Training Program and track TREC Fellows career development; and (3) to disseminate the TREC Training sessions, webinars and newsletter to the broader community of investigators. Conclusions: To our knowledge, no other in-residence training program exists that focuses on energetics and cancer research. Our vision is to continue the TREC mission of training scientists and clinicians to develop a cadre of well-trained, diverse researchers. The overall impact of this transdisciplinary training course will be defined by the degree to which TREC Fellows produce innovative research approaches and discoveries, thereby accelerating the dissemination and implementation of evidence-based approaches into everyday practice and patient care and improving the health of the population at risk for cancer as well as cancer survivors.
Unexpected Detection of Skeletal Muscle Renal Cell Carcinoma Metastasis With 99mTc-EDDA/HYNIC-Tyr3-Octreotide (Tektrotyd) Scan
Authors: Valentina Fuoco, Marta Barisella, Alice Lorenzoni, Elena Verzoni, Marco Maccauro
Journal: Clinical Nuclear Medicine (2022)

Abstract Somatostatin receptor scintigraphy with 99m Tc-Tektrotyd is widely used for the investigation of neuroendocrine tumors. Overexpression of somatostatin receptors has been shown in different tumor types including lymphomas, breast carcinoma, and renal cell carcinoma (RCC). Isolated case reports have shown that RCC metastases can be identified using somatostatin receptor imaging such as Octreoscan scintigraphy and 68 Ga-DOTATATE PET/CT. We report the case of a 70-year-old man with a history of surgically removed RCC who referred to 99m Tc-Tektrotyd scintigraphy for the evaluation of a pancreatic tail lesion. The scan revealed intense tracer uptake in a left splenius cervicis muscle lesion that on biopsy was consistent with metastatic RCC.
GCT-10. Successful Salvage of Relapsed intracranial Non-Germinaoteous Germ Cell Tumors NGGCTs in a Child With Renal Insufficiency with Novel platinum-Free chemotherapy Regimen
Authors: Nahla Ali Mobark, Musa Alharbi, Walid Ballourah, Abdulrahman AlSultan, Fahad Al Manjomi, Fahad Alotabi, Ali Abdullah O Balbaid, Mohammed Rayis, Zaid G AlNaqib, Wael abdel Rahman Aljabarat, Jonathan L Finlay
Journal: Neuro-Oncology (2022)

Abstract The Outcome for relapsed NGGCT is poor. Salvage therapy usually consist of reinduction platinum-based chemotherapy regimen followed by high-dose-chemotherapy and autologous-stem-cell-rescue (HDC/AuSCR) and re-irradiation with no consensus on optimal management and usually associated with remarkable toxicity. We present a 12-year-old boy diagnosed with a localized pineal Non-Germinaoteous Germ Cell Tumors NGGCTs of mixed origin with elevated AFP he had ETV and biopsy started on COG ACNS0122 protocol after receiving first cycle (carbo/Etoposide) he developed acute renal failure investigation showed small dysplastic kidney to avoid nephrotoxicity of platinum agents chemotherapy changed to VBE (Vinblastine, Bleomycin and Etoposide) post 3rd cycle MRI showed increase in size of the pineal mass with normal tumor markers representing Growing Teratoma Syndrome He had total surgical resection of the tumor Pathology showed predominant teratoma component He received radiation therapy CSI then another 3 cycles of VBE 4 months following treatment completion he presented with elevated AFB and new right anterior temporal lesion Spinal MRI and CSF were negative. He had 2 cycles of Salvage Non-nephrotoxic 4-drug regimens GEMPIV Gemcitabine 800 mg/m2 days 1 and 14. Paclitaxel 80 mg/m2 days 1 and14, Irinotecan 50 mg/m2 daily for 5 days Vinblastine 6 mg/m2 weekly days 1,8,14 MRI after 2 cycles showed remission with undetectable AFP then 2 consolidation cycles of etoposide and thiotepa (HDC/AuSCR) The 3rd consolidation cycles were cancelled due to hematological toxicity During treatment phases chemotherapy was well tolerated doses were adjusted according to his GFR with renal conservative and supportive therapy.post (HDC/AuSCR) he experienced delayed hematological recovery with persistent thrombocytopenia responded to Eltrombopag then he had focal Temporal lobe irradiation Currently patients in remission with chronic stage 3 renal Insufficiency Conclusions: this case showed that relapsed intracranial NGGCT can be successfully salvaged without platinum-based chemotherapy in patients with renal insufficiency.
Risk of cancer in young and older patients with congenital heart disease and the excess risk of cancer by syndromes, organ transplantation and cardiac surgery: Swedish health registry study (1930–2017)
Authors: Christina Karazisi, Mikael Dellborg, Karin Mellgren, Kok Wai Giang, Kristofer Skoglund, Peter Eriksson, Zacharias Mandalenakis
Journal: The Lancet Regional Health - Europe (2022)

Increasing survival of patients with congenital heart disease (CHD) will result in an increased risk of age-dependent acquired diseases later in life. We aimed to investigate the risk of cancer in young and older patients with CHD and to evaluate the excess risk of cancer by syndromes, organ transplantation and cardiac surgery.
LINC-09. Coexisting glioneuronal tumor and adrenal ganglioneuroma
Authors: Ataollah Shahbandi, Saeid Atashpanjeh, Aileen Azari-Yam, Farideh Nejat, Zohreh Habibi
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: While both glial/glioneuronal neoplasia and ganglioneuroma have been reported as components of multiple primary neoplasms, no patient has been diagnosed with multiple primary neoplasms of cerebral glial/glioneuronal tumors with oligodendroglioma-like features and adrenal ganglioneuroma up to now. CASE: A previously healthy five-year-old girl was admitted with a two-week history of headaches and vomiting. Brain Magnetic resonance imaging (MRI) showed a massive heterogenous multi-cystic enhancing lesion in the right temporoparietal area with substantial vasogenic edema. The patient underwent craniotomy and tumor gross total resection. The intra-operative histomorphological assessment of the tumor was well-matched with a glial tumor. The patient developed systolic hypertension during postoperative care in the Intensive Care Unit. Subsequent abdominal CT scan unveiled a calcified mass of the left adrenal gland origin. Blood and urine catecholamine tests, vanillylmandelic acid (VMA), were within the normal range. The surgical excision specimen exhibited a clear cell neoplasm with diffuse infiltrative growth. A distinguishing combination of oligodendroglioma-like perinuclear haloes, clear cell appearance and vascular proliferation rendered the diffuse Glioneuronal tumor with Oligodendroglioma-like features. With the combination of oligodendroglial-like appearance, negative 1p/19q codeletion, Wild IDH, no BRAF mutation, weak GFAP, and positive synaptophysin altogether, the tumor was compatible with the novel diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC). The patient underwent laparotomy and tumor resection subsequently. Morphologic histopathological examinations of the adrenal mass were in line with ganglioneuroma. After discharge, no pathological uptake was identified with iodine-131 meta-iodobenzylguanidine scan (MIBG scan). No tumor residue was apparent on postoperative brain MRI. The patient received no adjuvant therapy for brain and adrenal tumors and underwent close surveillance for both tumors. No clinical or radiologic recurrence was recognized after six months of follow-up. CONCLUSIONS: Concurrent glioneuronal tumor and ganglioneuroma can be managed safely when diagnosed timely, leading to favorable outcomes.
Exploring "the healthy immigrant effect" among elderly Asian patients with cancer: A nationwide population-based assessment.
Authors: Manan Nayak, Paul Nguyen, Ilana Braun, Russell K. Schutt
Journal: Journal of Clinical Oncology (2022)

10567 Background: Asian Americans are the fastest-growing immigrant group in the U.S. As the oldest immigrant group on average, they are at heightened risk for cancer and other diseases. This study explored whether the risk is mitigated by the healthy immigrant effect (HIE), an epidemiological phenomenon that has been well documented among Latino immigrants. Evidence of a healthy immigrant effect among Asians as a whole or in specific Asian subgroups is limited, and almost none focus on the elderly with a cancer diagnosis. This original research study examines the evidence for an HIE in a large ethnically diverse sample of elderly persons with a cancer diagnosis. Methods: This is a retrospective observational study utilizing data collected across 14 regions of the U.S. SEER-Medicare Health Outcomes Survey (SEER-MHOS), a linked dataset sponsored by the NCI and the Center for Medicare &amp; Medicaid Services. Logistic regression analyses were conducted to examine HIE among Asians in the aggregate and subgroups of Asians for smoking and body mass index (BMI), using survey language and ethnic concentration as proxies for nativity. Results: Asians, in the aggregate, had comparable social backgrounds and had better health behaviors (i.e., lower smoking and BMI) than non-Hispanic Whites. When Asians were disaggregated, Hawaiians and Japanese had higher smoking and obesity rates than Chinese. A protective effect was observed among Asians in the aggregate living in an ethnic enclave with lower smoking prevalence and lower BMI. Chinese respondents opting to complete surveys in their native language or living in ethnic enclaves were less likely to be overweight, but no significant associations were found in relation to their smoking. Conclusions: Support for a healthy immigrant effect was largely consistent for Asians in the aggregate with respect to both language and ethnic concentration, but support was mixed among subgroups of Chinese patients. The presence of the HIE suggests that the health status and needs of recent Asian immigrants seeking oncologic care may be different than Asians who have been in the U.S. longer. These findings suggest a need for community-based efforts to encourage preservation of a healthier living style observed among first-generation immigrants.
Combination of transarterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) compared to TACE alone as bridging therapy transplant recipients with hepatocellular carcinoma: An update.
Authors: Abdullah Esmail, David Victor, Sudha Kodali, Edward A. Graviss, Duc T. Nguyen, Linda W. Moore, Ashish Saharia, Robert McMillan, Joy N. Fong, Ahmed Uosef, Mahmoud Elshawwaf, Kirk Heyne, Rafik Mark Ghobrial, Maen Abdelrahim
Journal: Journal of Clinical Oncology (2022)

e16201 Background: Hepatocellular carcinoma (HCC) is the world's sixth most prevalent cancer and the third leading cause of cancer-related death. For patients with advanced HCC, trials combining TACE with tyrosine kinase inhibitors (TKIs) such as Sorafenib have given mixed outcomes. (TACE) plus lenvatinib led showed significant improvement in OS compared to lenvatinib alone in the first-line setting in patients with advanced HCC according to phase 3 LAUNCH trial which was presented at the 2022 ASCO Gastrointestinal Cancers Symposium. This study was aimed to compare the outcome of HCC patients who received TACE plus TKI agent versus TACE alone. Methods: Retrospectively all subjects with unresectable HCC were included in this study, who underwent liver transplantation (LT) and were treated by either TACE alone (TA) or TACE plus Sorafenib (TandS) between July 2008–December 2021. For categorical factors, HCC recurrence after LT was reported as frequencies and proportions, while for continuous variables, the median and interquartile range (IQR) or mean was used. For categorical variables, Chi-square or Fisher's exact tests were used, while for continuous variables, Kruskal-Wallis test was used. Results: Seven hundred patients were screened; only 128 patients in total underwent LT with most being males (77%); the median age of 61.5 years. The TA group included 79 (77%) subjects who matched Milan Criteria (MC) and 24 (23%) who did not, but the TandS group had a greater number of cases who did not meet MC: 16 (64%) versus 9 (36%); p = 0.01. There was a significant variation in five-year disease-free survival (DFS) across the therapy groups investigated, with 100% DFS in the TandS group vs 67.2 percent in the TAne group (p = 0.07). The TandS group had a five-year patient survival rate of 77.8% compared to 61.5 percent in the TA group (p = 0.51). However, beyond the MC, patients who were treated with TA had the average percentage of necrotic tumor on resected histology of 43.8 %, 32 % compared to 69.6 %, 32.8 % for cases treated with TandS, p = 0.03. Conclusions: We have found that using TandS is generally well tolerated and demonstrated improved OS compared to TA in patients with unresectable HCC. A prospective clinical study (NCT05171335) is ongoing at our institution to further investigate this concept.
IMMU-10. TUMOR ASSOCIATED MYELOID CELLS DRIVE THE IMMUNOBIOLOGY OF HIGH RISK PEDIATRIC EPENDYMOMA
Authors: Andrea Griesinger, Kent Riemondy, Nithyashri Eswaran, Andrew Donson, Nicholas Willard, Simon Paine, Georgia Bowes, John Rheaume, Rebecca Chapman, Judith Ramage, Andrew Jackson, Richard Grundy, Nicholas Foreman, Timothy Ritzmann
Journal: Neuro-Oncology (2022)

Abstract Molecular profiling of pediatric ependymoma (EPN) has previously identified discrete neoplastic subpopulations, of which Mesenchymal EPN Cells (MEC) characterize Posterior Fossa A tumors (PFA). MECs are associated with tumor immunosuppression. Here we further characterize the EPN immune environment using single-cell sequencing, spatial phenotyping and cytokine analyses to better define infiltrating myeloid subpopulations. We hypothesize that neoplastic and myeloid cells interact to propagate an immune suppressive environment conferring resistance to traditional therapies. We delineated myeloid cell subpopulations from single-cell RNA-seq of 26 pediatric EPNs and validated them through deconvolution of bulk gene expression profiling (n=299). To define subpopulation spatial distribution, we interrogated a range of tumor and myeloid markers using multiplex immunofluorescence (mIF). Finally, using single-cell cytokine analyses, we gained further insight into myeloid subpopulation function. Eight distinct myeloid subpopulations were identified, relating to macrophages, microglia and monocytes. A subpopulation of cells with wound healing ontologies and characterized by TREM1 expression, demonstrated features of myeloid derived suppressor cells, including IL6/STAT3 pathway activation. We called these hypoxia-M. Like MEC neoplastic cells, hypoxia-M was associated specifically with PFA1 subgroup EPN in both single-cell and bulk tumor gene expression profiling (p&amp;lt;0.001). Additionally, the presence of MEC and hypoxia-M correlated strongly in gene expression (r2=0.92, p&amp;lt;0.001) and IHC analyses, where they co-located to borders between necrosis, blood vessels and viable tumor. Analysis using mIF (n=54) confirmed MEC/hypoxia-M co-location and highlighted that all types of immune cell corralled in significant numbers around areas of vasculature and necrosis. Single cell cytokine analyses demonstrated that hypoxia-M secrete IL-8 which, we hypothesize, amplify the pro-tumor phenotype in PFA1 tumor microenvironment. EPN is characterized by discrete myeloid cell subpopulations which contribute to the tumor microenvironment. Treatment strategies must focus on modifying this pro-tumor, immunosuppressive microenvironment to deliver more effective treatment for childhood ependymoma.